Brain circuits controlling appetite and body weight

What do we already know?

After a meal is ingested, the brain evaluates the energetic contents of food and relays this information via neuronal circuits connecting the brain with the periphery.  However, our understanding of how the brain controls energy balance remains largely unknown. 

What are we doing?

  • We are using state-of-the art genetic technologies to investigate the underlying neuronal networks that regulate appetite and the associated neurochemicals, with the ultimate aim of developing new therapeutics.
  • We focus on the nucleus of the solitary tract (NTS), a critical caudal brainstem region through which peripheral metabolic information enters the brain.

We aim to:

  • Define a comprehensive functional map of NTS circuits specifically regulating ingestive behaviour and energy homeostasis.
  • Characterise the anatomical organisation and the genetic fingerprint of NTS neurons that specifically modulate appetite.
  • Clarify how and when metabolic demands recruit NTS neurons in vivo and the specific energetic signals that modulate these cells.
  • Determine which NTS circuits are crucial in maintaining energy homeostasis and whether their impairment could promote metabolic diseases.
  • Burke, LK., Ogunnowo-Bada, E., Georgescu, T., Cristiano, C., Martinez De Morentin, PB., Valencia-Torres, L., D'Agostino, G., Riches, C., Heeley, N., Ruan, Y., Rubinstein, M., Low, MJ., Myers, MG., Rochford, JJ., Evans, ML. & Heisler, LK. 'Lorcaserin improves glycemic control via a melanocortin neurocircuit'. Molecular Metabolism.
    [Online] DOI: 10.1016/j.molmet.2017.07.004
  • Marcinkiewcz, CA., Mazzone, CM., D'Agostino, G., Halladay, LR., Hardaway, JA., DiBerto, JF., Navarro, M., Burnham, N., Cristiano, C., Dorrier, CE., Tipton, GJ., Ramakrishnan, C., Kozicz, T., Deisseroth, K., Thiele, TE., McElligott, ZA., Holmes, A., Heisler, LK. & Kash, TL. (2016). 'Serotonin engages an anxiety and fear-promoting circuit in the extended amygdala'. Nature, vol 537, 19318, pp. 97-101.
    [Online] DOI: 10.1038/nature19318
    [Online] AURA: Tom_27sNATURE_4_merged_1469007630.pdf
  • Martin-Gronert, MS., Stocker, CJ., Wargent, ET., Cripps, RL., Garfield, AS., Jovanovic, Z., D'Agostino, G., Yeo, GSH., Cawthorne, MA., Arch, JRS., Heisler, LK. & Ozanne, SE. (2016). '5-HT2A and 5-HT2C receptors as hypothalamic targets of developmental programming in male rats'. Disease Models & Mechanisms, vol 9, no. 4, pp. 401-412.
    [Online] DOI: 10.1242/dmm.023903
    [Online] AURA: 401.full.pdf
  • D'Agostino, G., Lyons, DJ., Cristiano, C., Burke, LK., Madara, JC., Campbell, JN., Garcia, AP., Land, BB., Lowell, BB., Dileone, RJ. & Heisler, LK. (2016). 'Appetite controlled by a cholecystokinin nucleus of the solitary tract to hypothalamus neurocircuit'. eLife, vol 5, 12225, pp. 1-15.
    [Online] DOI: 10.7554/eLife.12225
    [Online] AURA: e12225_download.pdf
  • Aviello, G. & D'Agostino, G. (2016). 'Tools for Controlling Activity of Neural Circuits Can Boost Gastrointestinal Research'. Frontiers in Pharmacology, vol 7, 43.
    [Online] DOI: 10.3389/fphar.2016.00043
    [Online] AURA: fphar_07_00043.pdf
  • Burke, LK., Doslikova, B., D'Agostino, G., Greenwald-Yarnell, M., Georgescu, T., Chianese, R., Martinez de Morentin, PB., Ogunnowo-Bada, E., Cansell, C., Valencia-Torres, L., Garfield, AS., Apergis-Schoute, J., Lam, DD., Speakman, JR., Rubinstein, M., Low, MJ., Rochford, JJ., Myers, MG., Evans, ML. & Heisler, LK. (2016). 'Sex difference in physical activity, energy expenditure and obesity driven by a subpopulation of hypothalamic POMC neurons'. Molecular Metabolism, vol 5, no. 3, pp. 245-252.
    [Online] DOI: 10.1016/j.molmet.2016.01.005
    [Online] AURA: 1_s2.0_S221287781600017X_main.pdf